Quercetin Enhances NAD+ Biosynthesis by Regulating NAMPT Expression

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor in mitochondrial respiration and play a crucial role as a redox carrier in various cellular processes. The oxidative form, NAD+, serves as a substrate for multiple crucial metabolic enzymes such as sirtuins and ADP-ribosyltransferases, making it an essential endogenous metabolite. Although NAD+ levels naturally decline with age, which may contribute to the development of aging-related diseases, it can be synthesized from daily dietary intake, which are important for maintaining its levels. In this study, we screened a panel of natural products using an NAD+-specific probe and identified several dietary supplements that elevate NAD+ levels. Notably, quercetin, a common flavonoid known for its antioxidant and senolytic effects, was shown to significantly enhance NAD+ levels both in vitro and in vivo. Quercetin enhances the expression of nicotinamide phosphoribosyltransferase (NAMPT), which is a crucial enzyme in NAD+ metabolism, by raising the level of histone acetylation in the promoter region of NAMPT. These findings highlight the potential of quercetin and other natural compounds to influence NAD+ metabolism, suggesting their possible use as dietary supplements or therapeutic options for aging and age-related diseases.